Performance of Xpert® MTB/RIF and Determine™ TB-LAM Ag in HIV-infected adults in peri-urban sites in Zambia.

SETTING: Peri-urban health facilities providing HIV and TB care in Zambia. OBJECTIVE: To evaluate 1) the impact of Xpert® MTB/RIF on time-to-diagnosis, treatment initiation, and outcomes among adult people living with HIV (PLHIV) on antiretroviral therapy (ART); and 2) the diagnostic performance of Xpert and Determine™ TB-LAM Ag assays. DESIGN: Quasi-experimental study design with the first cohort evaluated per standard-of-care (SOC; first sputum tested using smear microscopy) and the second cohort per an algorithm using Xpert as initial test (intervention phase; IP). Xpert testing was provided onsite in Chongwe District, while samples were transported 5-10 km in Kafue District. TB was confirmed using mycobacterial culture. RESULTS: Among 1350 PLHIV enrolled, 156 (15.4%) had confirmed TB. Time from TB evaluation to diagnosis (P = 0.018), and from evaluation to treatment initiation (P = 0.03) was significantly shorter for IP than for SOC. There was no difference in all-cause mortality (7.0% vs. 8.6%). TB-LAM Ag showed higher sensitivity with lower CD4 cell count: 81.8% at CD4 < 50 cells/mm3 vs. 31.7% overall. CONCLUSION: Xpert improved time to diagnosis and treatment initiation, but there was no difference in all-cause mortality. High sensitivity of Determine TB-LAM Ag at lower CD4 count supports increased use in settings providing care to PLHIV, particularly with advanced HIV disease.

High prevalence of tuberculosis in newly enrolled HIV patients in Zambia: need for enhanced screening approach.

SETTING: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed. OBJECTIVE: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees. DESIGN: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively. RESULTS: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/µl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific. CONCLUSIONS: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.

Derivation of a tuberculosis screening rule for sub-Saharan African prisons.

SETTING: Lusaka Central Prison, Zambia. OBJECTIVE: To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program. DESIGN: We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values. RESULTS: The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden. CONCLUSION: Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

Spread of drug-resistant pulmonary tuberculosis in Estonia.

Restriction fragment length polymorphism (RFLP) analysis of 209 Mycobacterium tuberculosis clinical isolates obtained from newly detected pulmonary tuberculosis patients (151 male and 58 female; mean age, 41 years) in Estonia during 1994 showed that 61 isolates (29%) belonged to a genetically closely related group of isolates, family A, with a predominant IS6110 banding pattern. These strains shared the majority of their IS6110 DNA-containing restriction fragments, representing a predominant banding pattern (similarity, >65%). This family A comprised 12 clusters of identical isolates, and the largest cluster comprised 10 strains. The majority (87.5%) of all multidrug-resistant (MDR) isolates, 67.2% of all isolates with any drug resistance, but only 12% of the fully susceptible isolates of M. tuberculosis belonged to family A. These strains were confirmed by spoligotyping as members of the Beijing genotype family. The spread of Beijing genotype MDR M. tuberculosis strains was also frequently seen in 1997 to 1999. The members of this homogenous group of drug-resistant M. tuberculosis strains have contributed substantially to the continual emergence of drug-resistant tuberculosis all over Estonia.

Tuberculosis as an occupational hazard for health care workers in Estonia.

SETTING: Tuberculosis incidence has been increasing in the Baltic states since the 1990s, accompanied by the emergence of drug resistance, including multidrug resistance (MDR). In this changing situation, the potential threat of nosocomial spread of tuberculosis to other patients and health care workers (HCW) has remained unrecognised. OBJECTIVE: To investigate the risk of tuberculosis in health care workers in Estonia. DESIGN: Cases of tuberculosis registered among HCWs from 1994 to 1998 were evaluated. The case records were analysed retrospectively and combined with bacteriological data including data on drug resistance. RESULTS: Sixty-seven HCWs (23 physicians, 23 nurses and seven laboratory technicians, 12 assistant nurses and two cleaners), all of whom tested negative for human immunodeficiency virus, were diagnosed as having active tuberculosis. The incidence of tuberculosis among HCWs (mean 91/100,000/year) was 1.5 to three times higher than in the general population. In a chest hospital in charge of regional tuberculosis care, the incidence was 30 to 90 times higher, and was highest among physicians. In 49 HCWs tuberculosis was confirmed by culture. Among these, drug resistance was detected in 23 (49%), 18 (38%) of whom had MDR tuberculosis. CONCLUSIONS: Health care workers, especially those working in a chest hospital where tuberculosis patients were treated, were found to be at an elevated risk of tuberculosis. MDR tuberculosis poses a particular threat which is difficult to combat.

Clinical outcomes of Estonian patients with primary multidrug-resistant versus drug-susceptible tuberculosis.

Little is known about the clinical outcomes of patients with primary multidrug-resistant (MDR) tuberculosis. Clinical outcomes among 46 patients in Estonia with primary MDR tuberculosis and 46 patients with pansusceptible tuberculosis were compared. Patients with MDR tuberculosis were more likely than those with pansensitive tuberculosis to have treatment failure (odds ratio, 8.9; 95% confidence interval [CI], 3.0-26.3) after adjusting for medical problems and weeks of effective treatment, often with second-line drugs. Ten patients (22%) with MDR tuberculosis and 2 (4%) with susceptible tuberculosis died of tuberculosis (P=.03). MDR tuberculosis (hazard ratio [HR], 7.8; 95% CI, 1.6-37.4), number of medical problems (HR, 2.5; 95% CI, 1.5-4.4), and male sex (HR, 5.8; 95% CI, 1.1-29.6) were associated with death due to tuberculosis in multivariable analysis. Human immunodeficiency virus test results were negative for all 55 patients tested. These findings underscore the urgent need for increased attention to prevention and treatment of MDR tuberculosis globally.

Drug resistant tuberculosis in Estonia.

SETTING: The incidence of drug resistant tuberculosis in Estonia has increased rapidly during the last five to six years. OBJECTIVE: To investigate the drug resistance patterns of Mycobacterium tuberculosis isolated from tuberculosis patients in Estonia. RESULTS: In 1994, 623 cases of tuberculosis were diagnosed in Estonia, 518 new cases with no previous history of tuberculosis, and 105 with a history of previous treatment for tuberculosis. All pulmonary M. tuberculosis isolates from 1994 were analysed for drug susceptibility. Of the 302 new cases (58.3%) that were culture verified, 28% had isolates resistant to one or more of the four drugs tested (isoniazid, rifampicin, streptomycin, ethambutol), and 9% had multi-drug resistant (resistant to at least isoniazid and rifampicin) strains. CONCLUSION: The incidence of drug resistance in M. tuberculosis is high in Estonia.